Dipeptidyl Peptidase-4 Inhibitors and the Risk of HF: Regression to the Truth?

Diabetes mellitus substantially increases the risk of death, ischemic events, and heart failure (HF), and patients with both diabetes mellitus and HF are at particularly elevated risk of cardiovascular death1. Although none of the diabetes cardiovascular outcome trials (CVOTs) have included HF events in their primary end point, HF outcomes appear to be the most distinctive, if not divisive, feature in these trials. Indeed, these outcomes appear to be heterogeneously affected by anti-hyperglycemic medications, including some concern regarding harm caused by thiazolidinediones, dual peroxisome proliferator-activated receptor α/γ agonists, and possibly sulfonylurea, weak evidence of benefit from historical trials with metformin, consistent benefit with sodium-glucose co-transporter 2 (SGLT2) inhibitors, and inconclusive results with glucagon-like peptide (GLP)-1 receptor agonists. The case of dipeptidyl peptidase-4 inhibitors (DPP-4i) is more complex. After years of post-UKPDS inertia, wandering, and glucose...